Company on track to report topline data from
AHFIRM in Q4 2023
CUPERTINO, Calif., Sept. 7,
2023 /PRNewswire/ -- DURECT Corporation (Nasdaq:
DRRX), a late-stage biopharmaceutical company pioneering the
development of epigenetic therapies to transform the treatment of
serious and life-threatening conditions, including acute organ
injury and cancer, today announced that the last patient has
completed the study protocol in the Company's AHFIRM trial.
AHFIRM is a Phase 2b randomized, double-blind,
placebo-controlled trial evaluating the safety and efficacy of
lasucosterol in subjects with severe alcohol-associated hepatitis
(AH). A total of 301 patients were randomized and dosed in AHFIRM
and DURECT plans to report topline data in the fourth quarter of
2023.
"We are pleased to have completed follow-up of all patients in
our Phase 2b AHFIRM trial, bringing us one step closer to
reporting topline data from the study which we anticipate in the
fourth quarter of 2023," stated James E. Brown, D.V.M.,
President and CEO of DURECT. "Assuming a positive outcome from
AHFIRM, we plan to review the results with the U.S. Food and Drug
Administration (FDA) in the first quarter of 2024. We
designed AHFIRM to be a potentially pivotal trial and hope to
expedite regulatory discussions through the Fast Track Designation
that the FDA previously granted. If approved, larsucosterol would
be the first FDA-approved treatment for alcohol-associated
hepatitis (AH) and would represent a paradigm shift in the
management of this life-threatening disease."
About the AHFIRM Trial
Enrollment was completed in June 2023 in our
Phase 2b randomized, double-blind, placebo-controlled,
international, multi-center study in subjects with severe acute
alcohol-associated hepatitis (AH) to evaluate saFety and effIcacy
of laRsucosterol treatMent (AHFIRM). The study is comprised of
three arms, and 301 total patients were randomized and dosed, with
approximately 100 patients in each arm: (1) Placebo plus supportive
care, with or without methylprednisolone capsules at the
investigators' discretion; (2) larsucosterol (30 mg); and (3)
larsucosterol (90 mg). Patients in the larsucosterol arms receive
the same supportive care without steroids. In order to
maintain blinding, patients in the two active arms receive matching
placebo capsules if the investigator prescribes steroids. The
primary outcome measure will be the 90-Day incidence of mortality
or liver transplantation for patients treated with larsucosterol
compared to those treated with placebo. The Company has enrolled
patients at clinical trial sites across the U.S., EU, U.K.,
and Australia. Reflecting the life-threatening nature of AH
and the lack of therapeutic options, the U.S. Food and Drug
Administration (FDA) has granted larsucosterol Fast Track
Designation for the treatment of AH. We believe a positive outcome
in the AHFIRM trial could support a New Drug Application filing.
For more information, refer to ClinicalTrials.gov Identifier:
NCT04563026.
About Alcohol-associated Hepatitis (AH)
AH is an acute form of alcohol-associated liver disease (ALD),
associated with long-term heavy intake of alcohol and often occurs
after a recent period of increased alcohol consumption (i.e., a
binge). AH is typically characterized by severe inflammation and
destruction of liver tissue (i.e., necrosis), potentially leading
to life-threatening complications including liver failure, acute
kidney injury and multi-organ failure. There are no FDA approved
therapies for AH and a retrospective analysis of 77 studies
published between 1971 and 2016, which included data from a total
of 8,184 patients, showed the overall mortality from AH was 26% at
28 days, 29% at 90 days and 44% at 180 days. A subsequent global
study published in December 2021, which included 85 tertiary
centers in 11 countries across 3 continents, prospectively enrolled
2,581 AH patients with a median Model of End-Stage Liver Disease
(MELD) score of 23.5, reported mortality at 28 and 90 days of
approximately 20% and 31%, respectively. Stopping alcohol
consumption is necessary, but frequently not sufficient for
recovery in many moderate (defined as MELD scores of 11-20) and
severe (defined as MELD scores >20) patients and therapies that
reduce liver inflammation, such as corticosteroids, are limited by
contraindications, have not been shown to improve survival at 90
days or one year, and have demonstrated an increased risk of
infection. While liver transplantation is becoming more common for
ALD patients, including AH patients, the total number of such
transplants is still relatively small. Average charges for a
liver transplant exceed $875,000, and patients require
lifelong immunosuppressive therapy to prevent organ rejection.
About Larsucosterol
Larsucosterol is an endogenous
sulfated oxysterol and an epigenetic modulator. Epigenetic
regulators are compounds that regulate patterns of gene expression
without modifying the DNA sequence. DNA hypermethylation, an
example of epigenetic dysregulation, results in transcriptomic
reprogramming and cellular dysfunction, and has been found to be
associated with many acute (e.g., AH) or chronic diseases (e.g.,
NASH). As an inhibitor of DNA methyltransferases (DNMT1, DNMT3a
and 3b), larsucosterol inhibits DNA methylation, which
subsequently modulates expression of genes that are involved in
cell signaling pathways associated with stress responses, cell
death and survival, and lipid biosynthesis. This may ultimately
lead to improved cell survival, reduced inflammation, and decreased
lipotoxicity. As an epigenetic modulator, the proposed mechanism of
action provides further scientific rationale for developing
larsucosterol for the treatment of acute organ injury and certain
chronic diseases.
About DURECT Corporation
DURECT is a biopharmaceutical company committed to transforming the
treatment of acute organ injury and chronic liver diseases by
advancing novel and potentially lifesaving therapies based on its
endogenous epigenetic regulator program. Larsucosterol, DURECT's
lead drug candidate, binds to and inhibits the activity of DNA
methyltransferases (DNMTs), epigenetic enzymes that are elevated
and associated with hypermethylation found in alcohol-associated
hepatitis (AH) patients. Larsucosterol is in clinical development
for the potential treatment of AH, for which FDA has granted a Fast
Track Designation; non-alcoholic steatohepatitis (NASH) is also
being explored. In addition, POSIMIR® (bupivacaine solution)
for infiltration use, a non-opioid analgesic utilizing the
innovative SABER® platform technology, is FDA-approved and has
been exclusively licensed to Innocoll Pharmaceuticals for
commercialization in the United
States. For more information about DURECT, please visit
www.durect.com and follow us on Twitter
https://twitter.com/DURECTCorp.
DURECT Forward-Looking Statements
This press
release contains forward-looking statements, including statements
made pursuant to the safe harbor provisions of the Private
Securities Litigation Reform Act of 1995, relating to: our plans to
report topline data in the fourth quarter of 2023, our plans to
meet with the FDA to review the results of AHFIRM trial in the
first quarter of 2024, the potential FDA approval of larsucosterol
for the treatment of AH, the ability of a positive outcome in the
AHFIRM trial to support a New Drug Application filing, our plans to
commercialize larsucosterol if approved, the commercialization of
POSIMIR by Innocoll, the potential to develop larsucosterol for AH,
NASH or other indications, and the potential benefits, if any, of
our product candidates. Actual results may differ materially from
those contained in the forward-looking statements contained in this
press release, and reported results should not be considered as an
indication of future performance. The potential risks and
uncertainties that could cause actual results to differ from those
projected include, among other things, the risks that the AHFIRM
trial takes longer to complete than anticipated, the risk that
ongoing and future clinical trials of larsucosterol do not confirm
the results from earlier clinical or pre-clinical trials, or do not
demonstrate the safety or efficacy of larsucosterol in a
statistically significant manner, the risk that the FDA or other
government agencies may require additional clinical trials for
larsucosterol before approving it for the treatment of AH even if
the results of the AHFIRM trial are successful, risks that Innocoll
may not commercialize POSIMIR successfully, and risks related to
the sufficiency of our cash resources, our anticipated capital
requirements and capital expenditures, our need or desire for
additional financing, our ability to obtain capital to fund our
operations and expenses and our ability to continue to operate as a
going concern. Further information regarding these and other risks
is included in DURECT's most recent Securities and Exchange
Commission (SEC) filings, including its annual report on Form 10-K
for the year ended December 31, 2022
and quarterly report on Form 10-Q for the quarter ended
June 30, 2023 under the heading "Risk
Factors." These reports are available on our website
www.durect.comunder the "Investors" tab and on the SEC's website at
www.sec.gov. All information provided in this press release and in
the attachments is based on information available to DURECT as of
the date hereof, and DURECT assumes no obligation to update this
information as a result of future events or developments, except as
required by law.
NOTE: POSIMIR® is a trademark of Innocoll Pharmaceuticals,
Ltd. in the U.S. and a trademark of DURECT Corporation outside of
the U.S. SABER® is a trademark of DURECT Corporation. Other
referenced trademarks belong to their respective owners.
Larsucosterol is an investigational drug candidate under
development and has not been approved for commercialization by the
U.S. Food and Drug Administration or other health authorities for
any indication.
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SOURCE DURECT Corporation